N-Caffeoyltryptamine, a Potent Anti-Inflammatory Phenolic Amide, Suppressed MCP-1 Expression in LPS-stimulated THP-1 Cells and Rats Fed a High-Fat Diet

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemokine critically involved in the pathophysiological progression of several inflammatory diseases including arthrosclerosis. N-caffeoyltryptamine is a phenolic amide with strong anti-inflammatory effects. Therefore, in this paper, the potential effect of N-caffeoyltryptamine on MCP-1 expression was investigated as a potential p38 mitogen-activated protein (MAP) kinase inhibitor in vitro and in vivo. At the concentration of 20 μM, N-caffeoyltryptamine significantly inhibited p38 MAP kinase α, β, γ and δ by 15–50% (p < 0.05), particularly p38 MAP kinase α (IC50 = 16.7 μM) and β (IC50 = 18.3 μM). Also, the pretreatment of the lipopolysaccharide (LPS)-stimulated THP-1 cells with N-caffeoyltryptamine (10, 20 and 40 μM) led to significant suppression of MCP-1 production by 10–45% (p < 0.05) in the cells. Additionally, N-caffeoyltryptamine was also able to significantly downregulate MCP-1 mRNA expression in the THP-1 cells (p < 0.05). On the basis of this strong inhibition in vitro, an animal study was conducted to confirm this inhibitory effect in vivo. Rats were divided into three groups (n = 8): a normal control diet (C), a high-fat diet (HF), or a high-fat diet supplemented with N-caffeoyltryptamine (2 mg per day) (HFS). After 16 weeks, blood samples were collected from the rats in each group, and MCP-1 levels were determined in plasma with other atherogenic markers (C-reactive protein and soluble E-selectin (sE-selectin)). As expected, the average MCP-1 levels of the HF group were found to be higher than those of the C group (p < 0.05). However, the MCP-1 levels of the HFS group were significantly lower than those of the HF group (p < 0.05), suggesting that N-caffeoyltryptamine could decrease MCP-1 expression in vivo. Related to other atherogenic markers such as C-reactive protein and sE-selectin, there was no significant difference in their levels between the HF and HFS groups. These data suggest that N-caffeoyltryptamine may specifically suppress MCP-1 expression in vitro and in vivo, possibly by inhibiting p38 MAP kinase.

Javamide-II Found in Coffee Is Better than Caffeine at Suppressing TNF-α Production in PMA/PHA-Treated Lymphocytic Jurkat Cells

“…However, there is currently little information available, although our preliminary data suggested that the C max could be around between 9 and 36 μM in plasma, and plausible concentrations in the gut may be around 900 μM, which is the case when 2 mg of safflomide, a javamide-II analogue, is provided to a 500 g rat. 35 Related to this, our preliminary data also suggested that some types of coffee may contain 1−10 mg per cup. On the basis of these data, less than 3 and 40 μM concentrations are estimated in the plasma and gut, respectively.…”

“…To validate the reported biological effects of javamide-II, information about the bioavailability and tissue distribution of javamide-II is much needed. However, there is currently little information available, although our preliminary data suggested that the C max could be around between 9 and 36 μM in plasma, and plausible concentrations in the gut may be around 900 μM, which is the case when 2 mg of safflomide, a javamide-II analogue, is provided to a 500 g rat . Related to this, our preliminary data also suggested that some types of coffee may contain 1–10 mg per cup.…”

Anti-Inflammatory and Antioxidant Effects of Regular Consumption of Cooked Ham Enriched with Dietary Phenolics in Diet-Induced Obese Mice

“…In this study, non-significant differences were observed through intervention in most of the cases, despite of PECH + HFD, which showed a slight, but significant reduction. The reduction of MCP-1 can result in a reduction of cardiovascular disease risk [ 58 ]. IL-1β is a pro-inflammatory cytokine produced by macrophages in response to TNF-α.…”